Effect of two pyrimidine analogs on accumulation of tubulin in NHIK 3025 cells.
Accumulation of tubulin as compared with the accumulation of total cellular protein in human NHIK 3025 cells treated with the sulfone 2-(2-thenyl)sulfonyl-5-bromopyrimidine (NY 4137) and the sulfoxide 2-(2-thenyl)sulfinyl-5-bromopyrimidine (NY 4138), two mitotic inhibitors, were investigated by two-parametric flow cytometry. Following a 4 h treatment with NY 4137 tubulin accumulation is inhibited while total protein continues to accumulate. After treatment for 4 h with NY 4138 the accumulation of total protein is approximately constant, while the accumulation of tubulin is reduced although not to the same degree as that found for NY 4137-treated cells. In addition, the percentage tubulin SH-groups (6.89 +/- 0.14) remaining after treatment of purified rat brain tubulin with NY 4137 or NY 4138 was determined. Treatment with 0.0125 mM NY 4137 reduced the number of tubulin SH-groups detectable with dithiobis benzoate or from 6.89 +/- 0.14 before treatment to about 4 after treatment. However, practically all SH-groups of tubulin remain detectable following treatment with the same concentration of NY 4138. From the results described in this report we infer that NY 4137 binds to tubulin SH-groups and that inhibition of tubulin accumulation follows as a secondary effect.
Juul
M E
ME
Department of Tissue Culture, Norwegian Radium Hospital, Montebello, Oslo.
Dornish
J M
JM
Juul
N O
NO
Pettersen
E O
EO
Oftebro
R
R
D000818:Animals; D001923:Brain Chemistry; D002460:Cell Line; D006801:Humans; D008938:Mitosis / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology*; D051381:Rats; D014404:Tubulin / Q000378:metabolism*
D011743:Pyrimidines; D014404:Tubulin; C047250:NY 4138; C051723:2-(2-thenyl)sulfonyl-5-bromopyrimidine